Universal Blood Test Could Predict Transplant Rejection

Scientists have identified a non-invasive method for determining whether a transplanted organ is failing in a patient, whether it is a kidney, liver, lung or heart.

For the first time, markers of dysfunction have been found to correspond across several types of transplanted organ. The finding raises the prospect of a blood test capable of diagnosing early rejection in all transplant settings – a tool that is not currently available.

With further research, the newly recognised biomarkers might also distinguish between different forms of organ rejection, including immune-related problems, poor blood supply and maladaptive repair processes.

Transplant rejection can threaten any organ

Long-term transplant survival varies by organ: the rate is 59 percent for lungs, 80 percent for livers, 82 percent for kidneys and 73 percent for hearts. Rejection may develop at any point after surgery, including many years afterwards, leaving patients with a lifelong risk.

Doctors generally begin to suspect transplant rejection when the affected organ shows signs of reduced function. Yet some patients have no symptoms before the organ fails, meaning an invasive biopsy is the only reliable way to establish what is happening.

Over recent years, several studies have explored whether evidence of organ rejection in a patient's blood or urine could be accessed more easily than through surgery. However, the potential biomarkers identified so far have not entered clinical practice, and they do not predict every form of organ rejection, typically detecting only one type.

Shared biomarkers across kidney, lung, liver and heart transplants

The present research is a meta-analysis intended to close that gap. Led by University of Sydney statistician Harry Robertson, its authors examined 54 datasets: 40 kidney transplant studies, 5 lung studies, 5 liver studies and 4 heart studies.

By comparing individual patients' blood samples with their biopsy results, the researchers found 158 genes that were differentially expressed during rejection across all four organs. That total is almost 20 times greater than would be expected by chance.

"This discovery is pivotal as it allows us to develop strategies to enhance the success rates of all transplants," explains Robertson.

Among the shared biomarkers are those involved in releasing proteins that activate white blood cells, enzymes that trigger cell death, cell receptors that permit materials to move in and out, and bone marrow cells participating in the immune response.

Robertson and colleagues say the results reveal a "unifying pan-organ molecular marker". Their approach "consistently outperformed" other organ-specific models that are now being adapted for clinical use.

It is still unclear, however, whether the method will also apply to pancreas, stomach or intestine transplants.

The team has created an interactive website through which scientists worldwide can compare potential transplant-rejection biomarkers with other methods, offering a much-needed standardised assessment.

"This atlas has led to the development of a proof of principle for a universal blood test that can predict the likelihood of transplant rejection before it occurs," Robertson says, "potentially setting a new standard in precision medicine and improving outcomes for transplant recipients worldwide."

Why earlier detection of organ rejection matters

Since 1989, the 1-year survival rate for kidney transplants – the most common type of organ transplant – has improved substantially, although long-term survival has not advanced to the same extent.

Part of the difficulty is that doctors still lack a straightforward, dependable way to assess the very earliest stages of organ rejection. At that point, drug treatment could help reduce problems before complete failure occurs and another transplant becomes necessary.

"I have noticed many of my patients feel constant anxiety - not knowing if their body is rejecting their transplanted organ or not," explained Northwestern Medicine transplant nephrologist, Lorenzo Gallon, who is studying ways to detect early rejection, in 2023.

"They may have waited years for a transplant and then finally received one from a loved one or deceased donor. Then, they spend the rest of their lives worrying about the health of that organ."

A dependable blood test for monitoring transplant rejection could improve that situation.

The study was published in Nature Medicine.